Protomer Alignment Modulates Specificity of RNA Substrate Recognition by Ire1

Overview

Journal Elife

Specialty Biology

Date 2021 Apr 27

PMID 33904404

Citations 4

Authors

Weihan Li

Kelly Crotty

Diego Garrido Ruiz

Mark Voorhies

Carlos Rivera

Anita Sil

R Dyche Mullins

Matthew P Jacobson

Jirka Peschek

Peter Walter

Affiliations

Soon will be listed here.

Abstract

The unfolded protein response (UPR) maintains protein folding homeostasis in the endoplasmic reticulum (ER). In metazoan cells, the Ire1 branch of the UPR initiates two functional outputs-non-conventional mRNA splicing and selective mRNA decay (RIDD). By contrast, Ire1 orthologs from and are specialized for only splicing or RIDD, respectively. Previously, we showed that the functional specialization lies in Ire1's RNase activity, which is either stringently splice-site specific or promiscuous (Li et al., 2018). Here, we developed an assay that reports on Ire1's RNase promiscuity. We found that conversion of two amino acids within the RNase domain of Ire1 to their counterparts rendered it promiscuous. Using biochemical assays and computational modeling, we show that the mutations rewired a pair of salt bridges at Ire1 RNase domain's dimer interface, changing its protomer alignment. Thus, Ire1 protomer alignment affects its substrates specificity.

Citing Articles

Endoplasmic Reticulum Membrane Homeostasis and the Unfolded Protein Response.

Ernst R, Renne M, Jain A, von der Malsburg A Cold Spring Harb Perspect Biol. 2024; 16(8.

PMID: 38253414 PMC: 11293554. DOI: 10.1101/cshperspect.a041400.

Fundamental and Applicative Aspects of the Unfolded Protein Response in Yeasts.

Ishiwata-Kimata Y, Kimata Y J Fungi (Basel). 2023; 9(10).

PMID: 37888245 PMC: 10608004. DOI: 10.3390/jof9100989.

Endoplasmic stress sensor Ire1 is involved in cytosolic/nuclear protein quality control in cells independent of .

Fauzee Y, Yoshida Y, Kimata Y Front Microbiol. 2023; 14:1157146.

PMID: 37415818 PMC: 10321714. DOI: 10.3389/fmicb.2023.1157146.

Evolutionary Aspects of the Unfolded Protein Response.

Mori K Cold Spring Harb Perspect Biol. 2022; 14(12).

PMID: 35940910 PMC: 9732898. DOI: 10.1101/cshperspect.a041262.

Stress-induced tyrosine phosphorylation of RtcB modulates IRE1 activity and signaling outputs.

Papaioannou A, Centonze F, Metais A, Maurel M, Negroni L, Gonzalez-Quiroz M Life Sci Alliance. 2022; 5(5).

PMID: 35193953 PMC: 8899846. DOI: 10.26508/lsa.202201379.

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